The prevalence and virility of nosocomial infections, coupled with the growing threat of antibiotic resistance and side effects of certain medications, highlight the urgent need for improved methods to safely and effectively prevent increasingly common multi-drug resistant infections. Medical facilities have reported increasing rates of nosocomial infections with major complications of burn injuries due to bacterial infections. Likewise, rising multi-drug resistance increases the risk and magnitude of infection in traumatic and surgical wounds. In the civilian setting in 2007, approximately 1.7 million people acquire a nosocomial infection while hospitalized, resulting in nearly 100,000 deaths annually. The majority of these infections are attributed to methicillin-resistant Staphylococcus aureus (MRSA). While hospitals have instituted improved hygiene habits for caregivers as well as MRSA admission screening protocols, these implementations have not effectively served to reduce the spread of nosocomial MRSA. In addition to the hospital environment, the close quarters of prisons and daycare centers may also facilitate elevated rates of nosocomial infections. The need for safe, prophylactic infection prevention is imperative to help control nosocomial infections and save lives. A rapid, cost-effective and nontoxic method of decontamination offers the greatest potential to reduce nosocomial infection. The Food and Drug Administration has recognized the bactericidal activity of chitosan. Research by our group has demonstrated an extremely broad-spectrum antimicrobial capability of chitosan-based materials, which indicates the potential to create non-toxic, efficacious, wide-ranging technologies to kill multi-drug resistant microorganisms in a variety of applications. Of key importance, because they are a fibrous polysaccharide that is not absorbed or metabolized by the body, these chitosan-based products are biocompatible.
Chitosan, a biopolymer derived from the second most abundant polymer on earth, chitin, has been widely used as a hemostatic bandage, cellular scaffold, and dietary supplement because it is biocompatible, biodegradable, and non-toxic. Chitosan has also shown antibacterial properties only present when dissolved in aqueous acidic solutions. In acid, the chitosan become polycationic, a property associated both with its solubility in acid as well as its antibacterial properties. We have developed chitosan based derivatives that readily dissolve in neutral water or saline which demonstrate enhanced antibacterial properties while maintaining the desirable characteristics of chitosan mentioned previously. These compounds will not require the area to be sealed during treatment and pose no threat to human health or the environment. In addition, the material can be stored as a dry powder or dissolved in water, saline, or other neutral solution with a long shelf life and dispersed when needed.
Multi-drug resistant Enterococci, Staphylococci and Pneumococci have become common nosocomial pathogens. These drug resistant organisms have been rapidly spreading by horizontal transfer of resistance elements and clonal spread through the medical system. Because these resistant organisms also form intractable biofilms on tissue and medical devices, deaths from these infections have been rising throughout the past two decades. More recently, community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) have been associated with increasingly virulent infections, including toxic shock syndrome (TSS), purpura fulminans and necrotizing fasciitis. Recent work with CA-MRSA strains has implicated Panton-Valentin leukocidin (PVL) as a major virulence determinant. See M. Labandiera-Rey et al., “Staphylococcus Aureus Panton-Valentine Leukocidin Causes Necrotizing Pneumonia,” 315 Science, 1130 (2007); B. Said-Salim et al., “Differential Distribution And Expression of Panton-Valentine Leucocidin Among Community-Acquired Methicillin-Resistant Staphylococcus Aureus Strains,” 43 J. Clin. Microbiol, 3373 (2005); J. Voyich et al., “Is Panton-Valentine Leukocidin The Major Virulence Determinant In Community-Associated Methicillin-resistant Staphylococcus Aureus Disease?” 194 J. Infect. Dis., 1761 (2006); and Loren G. Miller et al., “Necrotizing Fasciitis Caused by Community-Associated Methicillin-Resistant Staphylococcus Aureus in Los Angeles,” 352 New England J. of Med., 1445, No. 14 (2005). Additionally, because of the rapid onset of these toxicoses, the use of traditional systemic antibiotics is frequently unhelpful.
Chitosan and chitosan derivative compounds demonstrate effective treatment of MRSA. Because chitosan is biodegradable, non-toxic and exhibits antibacterial activity against a broad spectrum of microorganisms, it has been utilized in the medical arena. However, the use of chitosan is limited because of its insolubility at neutral and physiological pH.